(1) outlines several sources of sequence diversity in antibodies:
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- N-nucleotide addition: Nucleotides removed at VH/DJ junction by exonucleases and new nucleotides added (no citation)
- P-diversity: Asymmetric nicking of hairpins at VH/DH junction to generate blunt ends that get ligated
- Movement of D-gene nucleotides into new reading frames. Occurs in mice but rare in humans
- Inversion of D-genes, though this basically doesn’t happen in humans
- Formation of VH-DH-DH-JH assemblies (two D genes), ref 22 found this happens in about 1 in 800 B cells and even lower in memory B cells. Ref 23 first suggested these
- Transfer of VDJ gene to other V genes by activation-induced deaminase (ref 27)
- “VH invasion”: replacement of entire VH region with new upstream VH gene, leading to longer CDRH3s. Also seen in light chains
1.
Rees AR. Understanding the human antibody repertoire. mAbs. 2020;12(1). Available from: https://doi.org/10.1080/19420862.2020.1729683